1. Field of the Invention
This invention relates to novel piperazine derivatives or pharmaceutically acceptable salts thereof and more particularly to such a piperazine derivative represented by the following formula (I): ##STR2## wherein R.sup.1 is a hydrogen atom or a lower alkyl group; R.sup.2 is a hydroxyl group, an aralkyloxy group, a lower alkoxy group containing 1-5 carbon atoms or a lower alkenyloxy group containing 3-5 carbon atoms; R.sup.3 is a hydrogen atom, or an aralkyloxy group, a lower alkoxy group containing 1-5 carbon atoms or a lower alkenyloxy group containing 3-5 carbon atoms; and R.sup.4 is a hydrogen atom or a lower alkoxy group containing 1-5 carbon atoms, provided that R.sup.2 is a group other than the lower alkoxy group containing 1-5 carbon atoms when both R.sup.3 and R.sup.4 are hydrogen atoms; or a pharmaceutically acceptable salt thereof.
Further, the invention is concerned with a process for preparing such derivative or ester and with a cerebral circulation-improving drug containing the same.
2. Description of the Prior Art
Glucose and oxygen, which are energy sources required for the activation of brain cells, are principally supplied by means of blood. Any disorder or ailment would occur when cerebral blood flow is suspended even for several seconds. For example, a thrombus which has formed in a cerebral vessel reduces the cerebral blood flow and hence induces cerebral apoplexy or the like. It has also been known that coagulation of platelets takes place in the course of thrombus formation.
Thus, in the last several years, there has been increased emphasis on the development of a medicine which could exhibit both a blood flow increasing effect and a platelet anti-coagulating effect so as to prevent or cure cerebral circulation insufficiency or failure.
The present inventor has carried out extensive research with a view toward developing such a medicine. As a result, it has been found that piperazine derivatives represented by the formula (I) above or salts thereof are effective to selectively vasodilate peripheral vessels, particularly at vertebrae, in increasing blood flow and suppressing platelet coagulation.
As prior art compounds structurally similar to the piperazine derivatives (I) of the present invention, there have been known 2-(4-diphenylmethylpiperazinyl)-1-phenylethanol [Sv. Zikolova and A. Florin, Tr. Nauchnoissled. Khim.-Farm. Inst., 8, 89-100 (1972)] and 2-(4-diphenylmethylpiperazinyl)-1-methyl-1-phenylethanol (Delalande S. A., Ger. Offen., 2,111,776). Both of the compounds are represented by the following formula (VII): ##STR3## wherein R is a hydrogen atom or a methyl group.
However, these publications are silent as to how the prior art compounds would exert an improved effect on celebral circulation. It has been confirmed from some tests conducted by the inventor that such compounds are only marginal in their vasodilating activity for peripheral vessels, as will be described hereinafter. Of noteworthy importance is the fact that the desired vasodilating effects for peripheral vessels are attributable to a specific configuration in which the piperazine derivative of the formula (I) has either one of hydroxy, aralkyloxy, lower alkoxy and lower alkenyloxy groups at the 4-position of the benzene ring of the phenethyl moiety. The present invention is based upon this discovery.